The aim of this study is to evaluate the antifibrotic effect of ring-type Sp1 decoy oligonucleotides (ODNs) through blocking the transcription of transforming growth factor (TGF)-beta 1 and its downstream target genes. In this experiment, the expression of TGF-beta 1, metalloproteinase (MMP)- 13, and fibronectin was decreased in the group with the treatment of the ring-type Sp1 decoy ODNs. Also, alpha-smooth muscle actin positive bronchial lining cells and alveolar epithelia] cells were observed, especially around the lesions of extracellular matrix (ECM) deposition. These findings provide evidences for the finding of pulmonary epithelial-mesenchymal transition (EMT) and the effectiveness of Sp1 transcription factor as a target for the gene therapy on lung fibrosis. (C) 2007 Elsevier Inc. All rights reserved.